Bioreactor and related methods

Abstract

An apparatus for culturing cells includes a bioreactor. The bioreactor may be modular and may include in a chamber a fixed bed, such as an unstructured or structured fixed bed (such as a spiral bed) for culturing cells, with a return column arranged centrally within the chamber. The modular bioreactor may include a plurality of structured fixed bed arranged in a stacked configuration. The modular bioreactor may include an outer casing forming a space for conditioning (e.g., insulating, heating, cooling) at least a chamber in which cells are cultured. The bioreactor may also include an impeller with radially curved blades, and may also suspend the impeller so that it may move from side-to-side and align with an external drive. Related methods are also disclosed.

The invention claimed is: 
     
       1. A bioreactor system comprising:
 a cell culture vessel comprising a first end, a second end, and at least one reservoir between the first and second ends; and 
 a cell culture matrix disposed in the at least one reservoir, the cell culture matrix comprising a structurally defined substrate comprising a plurality of woven layers with surfaces configured for adhering cells thereto, 
 wherein the substrate is disposed within the at least one reservoir in a wound configuration, and 
 wherein the plurality of woven layers of the substrate are not separated by a spacer material. 
 
     
     
       2. The system according to  claim 1 , wherein the plurality of woven layers are in contact. 
     
     
       3. The system according to  claim 1 , further including at least one external reservoir and conduits for circulating fluid between the at least one external reservoir and the cell culture vessel. 
     
     
       4. The system according to  claim 3 , wherein a first conduit of the conduits is connected to a port in a lid of the cell culture vessel. 
     
     
       5. The system according to  claim 1 , wherein the at least one reservoir of the cell culture vessel includes a first chamber including the cell culture matrix, the first chamber having an fluid input end and a fluid output end. 
     
     
       6. The system according to  claim 5 , wherein the at least one reservoir further includes a second chamber concentric with the first chamber and defined by an imperforate wall for returning fluid having passed through the cell culture matrix from the fluid input end to the fluid output end back to the fluid input end of the first chamber. 
     
     
       7. The system according to  claim 6 , wherein the layers of the cell culture matrix are wound around the imperforate wall. 
     
     
       8. The system according to  claim 6 , the at least one reservoir of the cell culture vessel further including a third chamber for receiving fluid for delivery to the cell culture matrix. 
     
     
       9. The system according to  claim 8 , wherein the third chamber is below the first chamber and includes an agitator. 
     
     
       10. The system according to  claim 8 , wherein the third chamber is above the first chamber. 
     
     
       11. The system of  claim 1 , the cell culture vessel further comprising an inlet and an outlet, wherein the bioreactor system is configured to flow material into the at least one reservoir via the inlet, through the at least one reservoir in a flow direction from the first end to the second end, and out of the at least one reservoir via the outlet. 
     
     
       12. The system of  claim 1 , wherein the substrate is disposed within the at least one reservoir as a cylindrical substrate at least partially surrounding a central longitudinal axis of the bioreactor vessel. 
     
     
       13. The system of  claim 12 , wherein a central longitudinal axis of the cylindrical substrate is parallel to the flow direction. 
     
     
       14. The system of  claim 1 , wherein the substrate and the at least one reservoir are configured such that the substrate contacts a wall of the at least one reservoir. 
     
     
       15. The system of  claim 1 , wherein the substrate is configured to be inserted into the reservoir through an opening in the cell culture vessel. 
     
     
       16. The system of  claim 1 , wherein the cell culture vessel comprises a support within the at least one reservoir configured to support the cell culture matrix therein. 
     
     
       17. The system of  claim 16 , wherein the substrate support comprises a support member extending from a first end of the cell culture vessel towards a second end of the cell culture vessel, wherein the wound substrate is configured to surround at least a portion of a circumference of the substrate support member such that the substrate support member is parallel to the central longitudinal axis of the wound substrate. 
     
     
       18. A bioreactor system comprising:
 a cell culture vessel comprising a first end, a second end, and at least one reservoir between the first and second ends; and 
 a cell culture matrix disposed in the at least one reservoir with surfaces configured for adhering cells thereto, the cell culture matrix comprising a structurally defined substrate; 
 wherein the substrate is disposed within the at least one reservoir in a wound configuration creating a plurality of woven layers of substrate in the wound configuration, and 
 wherein the cell culture matrix comprises the woven cell culture substrate without any other solid material between adjacent surfaces of the cell culture substrate. 
 
     
     
       19. The system of  claim 18 , the cell culture vessel further comprising an inlet at the first end and an outlet at the second end, wherein the bioreactor system is configured to flow material into the at least one reservoir via the inlet, through the at least one reservoir in a flow direction from the first end to the second end, and out of the at least one reservoir via the outlet. 
     
     
       20. The bioreactor system of  claim 18 , wherein the at least one reservoir defines a single flow path for material to flow in the flow direction from the first end to the second end. 
     
     
       21. A bioreactor system comprising:
 a cell culture vessel comprising a first end, a second end, and at least one reservoir between the first and second ends; and 
 a cell culture matrix disposed in the at least one reservoir, the cell culture matrix comprising a structurally defined substrate including a plurality of layers of woven material without another layer of material between adjacent surfaces of the plurality of layers of woven material. 
 
     
     
       22. The system according to  claim 21 , wherein the plurality of layers of woven material are stacked in the cell culture vessel. 
     
     
       23. The system according to  claim 21 , wherein the substrate is wound to form the plurality of layers of woven material. 
     
     
       24. An apparatus for culturing cells in connection with a fluid flow, comprising:
 a bioreactor including a structured fixed bed for culturing cells, the bioreactor comprising a housing forming an interior compartment, the interior compartment including the structured fixed bed for culturing cells, wherein the structured fixed bed comprises a plurality of layers of woven material in direct contact with one another; and 
 an external reservoir and conduits for circulating fluid to the bioreactor.